JP6977987B2 - Magnetic field measuring device and magnetic field measuring method - Google Patents

Description

The present invention relates to a magnetic field measuring device and a magnetic field measuring method for detecting an object to be measured by a magnetic immunological test, and specifically, to a magnetic substance (magnetic marker) bonded to the substance to be measured in a liquid. The present invention relates to a magnetic field measuring device and a magnetic field measuring method for measuring a magnetic field derived from the magnetic field.

Immune tests that detect biological substances such as disease-derived proteins and pathogens are used in medical diagnosis. In the immunological test, an antigen-antibody reaction in which an antigen and an antibody to be measured specifically bind to each other is used, and this antibody is labeled with a substance called a marker to detect a signal from the marker of the antibody bound to the antigen. By doing so, it becomes possible to measure the amount of the antigen.

As one of the immunological tests, an antibody having a known binding ability to a substance to be measured is labeled with an optical marker such as a fluorescent enzyme, and the degree of binding to the substance to be measured is optically detected by optical immunity. Inspection is being carried out. Here, many optical immunological tests require a cleaning and removing step for separating the optical marker bound to the substance to be measured and the optical marker not bound to the substance to be measured, which is complicated and time-consuming. There are sides.

On the other hand, unlike the optical immunoassay, a technique for detecting a substance to be measured by a magnetic method is known as a magnetic immunoassay (Patent Documents 1 and 2). Magnetic immunoassay is a method of detecting an antigen-antibody reaction using magnetic particles and a magnetic sensor. Magnetic particles (hereinafter referred to as magnetic markers) are added to the antibody to label the antibody, and the antigen is the substance to be measured. The degree of coupling with the magnetic marker is detected by using a magnetic sensor. Specifically, a sample in which a substance to be measured and an antibody to which a magnetic marker is added is bound in a solution is prepared, and a DC magnetic field is applied to the sample from the outside to magnetize the magnetic marker. The magnetic marker-added antibody (hereinafter referred to as a binding marker) bound to the substance to be measured after blocking the application of the DC magnetic field has a larger volume than the magnetic marker-added antibody (unbound marker) not bound to the substance to be measured. Therefore, the brown rotation movement is slow, so the brown relaxation time is relatively slow. This allows the coupling marker to have residual magnetism for a long time.

On the other hand, an antibody with a magnetic marker (unbound marker) that did not bind to the substance to be measured is also present in the solution. Since the unbound marker exists alone, the particle size is small and the brown rotational motion becomes fast. Therefore, the unbound marker antibody tends to have a random direction of the magnetic moment, the brown relaxation time is fast, and the unbound marker has a short residual magnetism. As a result, the magnetic signal of only the coupled marker can be selectively detected by utilizing the difference in brown time between the coupled marker and the unbound marker.

As described above, the magnetic immunoassay measures the degree of binding to the substance to be measured by utilizing the difference in the brown relaxation characteristics of the magnetic marker without performing the step of washing and removing the magnetic marker-added antibody. Can be done.

Patent Document 1-5 discloses a configuration in which a SQUID (Superconducting Quantum Interference Device) is used as a magnetic sensor to detect a magnetic signal based on brown relaxation of a magnetic marker.

Further, Patent Document 6 discloses a magnetic field measuring device that measures the brown relaxation characteristic of a magnetic marker as a difference in AC magnetic susceptibility by using a magnetoresistive effect element (MR sensor). That is, a larger volume coupling marker has lower followability to a high frequency AC magnetic field than a smaller volume uncoupled marker, and the AC magnetic susceptibility depends on frequency and brown relaxation time. From this, the amount of the coupling marker can be measured by measuring the AC magnetic susceptibility using a magnetoresistive effect element (MR sensor).

Further, Patent Document 7 discloses a magnetic foreign matter inspection device that detects the presence or absence of magnetic foreign matter in an inspection object by using a thin film magnetic sensor (magnetic resistance sensor, magnetic impedance sensor) having directionality in the magnetic field detection direction. ..

Japanese Unexamined Patent Publication No. 2015-163846 Japanese Unexamined Patent Publication No. 2007-240349 Japanese Unexamined Patent Publication No. 2009-115529 Japanese Unexamined Patent Publication No. 1-112161 Japanese Unexamined Patent Publication No. 2001-033455 Japanese Patent No. 5560334 Japanese Unexamined Patent Publication No. 2014-159884

Although the device using the SQUID (Superconducting Quantum Interference Device) disclosed in Patent Document 1-5 enables highly sensitive detection of the residual magnetic signal of the coupling marker magnetized by the DC magnetic field. The configuration including the cooling device and the vacuum device is complicated and large-scale, and the device is expensive.

Further, the magnetic field measuring device disclosed in Patent Document 6 makes it possible to detect the coupling marker from the frequency characteristic of the AC magnetic susceptibility, but the detection by the magnetoresistive element (MR sensor) has relatively low sensitivity and a very small amount. There is a problem that it is difficult to detect the coupling marker with high sensitivity. Further, Patent Document 7 does not describe the use of the brown relaxation characteristic, and it is not possible to detect the bound marker and the unbound marker separately.

Therefore, an object of the present invention is to provide a magnetic field measuring device and a magnetic field measuring method capable of performing a magnetic immunoassay with higher sensitivity by a novel method and a relatively simple configuration.

The magnetic field measuring device of the present invention for achieving the above object synchronizes with a moving mechanism that orbits a container containing a sample containing a magnetic substance and an object to be measured that can be bonded to the magnetic substance, and a rotation cycle of the container. The magnetic field that reverses and switches in the direction of the magnetic field at each round is separated from the magnetic field generator applied to the sample contained in the orbiting container to the extent that it is not substantially affected by the magnetic field from the magnetic field generator. It is equipped with a magnetic field sensor that detects a signal corresponding to a magnetic field emitted from a sample housed in a position and orbiting container, and the magnetic field sensors are arranged in parallel in a direction orthogonal to the rotation direction of the container. The moving mechanism includes the magnetic material collected and aggregated in the container and the object to be measured bonded to the magnetic material. It is characterized in that the container is circulated so as to pass directly above one of the sensor elements and not to pass directly above the other .

In the above, the magnetic field measuring device of the present invention further includes an arithmetic processing unit that determines the amount of the object to be measured based on the difference value of the signals detected by two adjacent movements in a plurality of movements. It is characterized by.

The magnetic field measuring method of the present invention is a step of magnetizing a sample containing a magnetic substance and a measured object that can be bonded to the magnetic substance by a DC magnetic field using a magnetizing magnet, and a container for accommodating the sample by a moving mechanism. a step of circulating a plurality of times, the magnetic field generator, and applying a magnetic field direction of the magnetic field switched by reversed each cycle in synchronization with the rotation period of the vessel, the sample contained in a container orbiting, The magnetic field sensor includes a step of detecting a signal corresponding to the magnetic field emitted from the sample contained in the orbiting container, and the magnetic field sensors are arranged in parallel in a direction orthogonal to the rotation direction of the container. It includes one sensor element and a bias magnet that applies a bias magnetic field to the sensor element, and the moving mechanism is such that the magnetic material collected and aggregated in the container and the object to be measured coupled with the magnetic material are sensor elements. It is characterized in that the container is orbited so as to pass directly above one and not directly above the other.

The magnetic field measuring method of the present invention is characterized by further comprising a step of determining the amount of the object to be measured based on the difference value of the signals detected by two adjacent movements in a plurality of movements. And.

According to the magnetic field measuring device and the magnetic field measuring method of the present invention, it is possible to perform a more sensitive magnetic immunoassay by utilizing the brown relaxation characteristic. A highly sensitive magnetic field measuring device can be configured relatively simply, compactly, and at low cost.

It is a figure which shows the schematic structural example of the magnetic field measuring apparatus in embodiment of this invention. It is a figure which shows the schematic arrangement example of the magnetic field sensor 40. It is a figure which shows the processing procedure of the magnetic field measurement method by the magnetic field measuring apparatus in embodiment of this invention. It is the schematic schematic diagram of the magnetic field measuring apparatus in embodiment of this invention. It is a figure which shows the positional relationship of the container which passes on the sensor element of a magnetic field sensor. It is a graph which shows the measurement data of the output voltage of a magnetic field sensor 40. It is a graph which shows the relationship of the adjacent voltage difference with respect to the amount of a polymer bead. It is a graph which shows the relationship of the adjacent voltage difference with respect to the number of caries-related bacteria (mutans bacteria).

Hereinafter, embodiments of the present invention will be described with reference to the drawings. However, such embodiments do not limit the technical scope of the invention.

FIG. 1 is a diagram showing a schematic configuration example of a magnetic field measuring device according to an embodiment of the present invention. In FIG. 1, the magnetic field measuring device rotates a rotation mechanism 20 that orbits a container 12 accommodating a sample 10 around a rotation axis, and a magnetic field whose magnetic field direction is switched at each rotation in synchronization with the rotation cycle of the container 12. The magnetic field generating unit 30 applied to the sample 10 housed in the container 12 is housed in the rotating container 12 arranged at a position separated from each other so as not to be substantially affected by the magnetic field from the magnetic field generating unit 30. It is configured to include a magnetic field sensor 40 for detecting a magnetic field emitted from the sample 10.

The rotation mechanism 20 has a rotation shaft 24 with a built-in motor attached to the base 22, and an arm portion 26 attached so as to extend radially from the rotation shaft 24, and the container 12 is held at the tip end portion of the arm portion 26. To. By rotating the rotating shaft by the motor, the container 12 held by the arm portion 26 rotates around the rotating shaft 24. The rotation mechanism 20 is not limited to the configuration of the rotation shaft and the arm, and may have a configuration having a disk plate that revolves around the rotation shaft. Further, the mechanism for periodically moving the container 12 for accommodating the sample 10 is not limited to the rotation mechanism, and another movement mode such as a reciprocating linear motion may be adopted. The container 12 contains a sample (sample) 10 which is a mixed solution of a magnetic substance (also referred to as magnetic beads) and an object to be measured that can be bonded to the magnetic substance.

The magnetic field generation unit 30 includes an oscillator 32 and a coil 34 that generates a magnetic field by controlling the oscillator 32, and the oscillator 32 controls the coil 34 to switch the magnetic field direction in synchronization with the rotation cycle of the rotation mechanism 20. The container 12 orbits directly above the coil 34, and its magnetic field direction is switched every time the container 12 orbits. That is, in the number of orbits of the container 12, the direction of the magnetic field applied to the sample 10 housed in the container 12 is opposite in the even number and the odd number. In addition, a permanent magnet 38 is placed to magnetize the sample 10.

The magnetic field sensor 40 is a magnetic impedance sensor (MI sensor) that detects a magnetic field by utilizing the magnetic impedance effect. The magnetic impedance effect is that when a high-frequency current is applied to a high magnetic permeability alloy magnetic material such as an amorphous alloy wire, the magnetic permeability in the circumferential direction changes significantly due to the application of an external magnetic field, and the skin depth changes. This is a phenomenon in which the impedance changes, and it is a sensor that can reduce the size, sensitivity, and power consumption of the magnetic sensor. As the magnetic field sensor 40, it is preferable to adopt an MI sensor from the viewpoint of miniaturization and high sensitivity of the device, but the present invention is not limited to this, and another sensor having a function of detecting a magnetic field such as a magnetic resistance sensor (MR sensor) is used. May be.

The signal processing unit 50 is a means for arithmetically processing the output signal (sensor voltage value) from the magnetic field sensor 40, converts the output signal of the analog signal into a digital signal, and arithmetically processes the digital signal with a predetermined arithmetic processing device. , The arithmetic processing and the determination processing described later are executed. The signal processing unit 50 is realized by a general-purpose computer device or a specific digital arithmetic circuit.

FIG. 2 is a diagram showing a schematic arrangement example of the magnetic field sensor 40. The magnetic field sensor 40 has two sensor elements 40a and 40b arranged in parallel in a direction orthogonal to the rotational movement direction of the container 12, and operates as a differential sensor. As will be described later, as a configuration of the differential sensor, background noise is generated by passing the container 12 directly above one element of the two sensor elements and preventing the container 12 from passing over the other element. It can be offset and the sensitivity can be increased. Further, a bias magnet 42 for applying a bias magnetic field to the sensor elements 40a and 40b is arranged close to the sensor elements 40a and 40b, and a bias magnetic field facing the rotational movement direction of the container 12 is applied. In order to accurately observe the brown relaxation, it is preferable to suppress the leakage magnetic field from this bias magnetic field as much as possible, and the influence of the magnetization of the magnetic beads contained in the sample 10 due to the bias magnetic field is reduced to a negligible level. A magnetic shield 44 is arranged between the rotating container and the bias magnet 42. The magnetic shield 44 is made of a soft magnetic material, and the rotating container 12 is arranged at a position close to the bias magnet 42 to block the magnetic field from the bias magnet 42.

FIG. 3 is a diagram showing a processing procedure of a magnetic field measuring method using a magnetic field measuring device according to an embodiment of the present invention. Further, FIG. 4 is a schematic schematic diagram of the magnetic field measuring device according to the embodiment of the present invention, and shows the same configuration as that of FIG.

(1) The sample 10 is placed in the container 12 and stirred (ultrasonic cleaning for about 15 seconds + vibration stirring for about 30 seconds), and set at a predetermined position on the arm portion 26 of the rotation mechanism 20 (S100). Sample 10 is a mixed solution of magnetic beads, which is a magnetic substance, and a substance to be measured that can be bound to the magnetic beads. The substance to be measured is a bacterium (including a model bacterium) to be detected, and the number of magnetic beads to be measured is adjusted to be larger than the number of substances to be measured (the maximum number assumed). Preferably, the sensitivity is increased by adjusting so as to reduce the number of unbound residual magnetic beads that do not bind to the substance to be measured. Polymer beads can also be used as a model bacterium when used in an experiment.

The initial position of the container 12 is a position directly above the coil 34 of the magnetic field generating portion 30. Stirring is preferably performed immediately before the measurement. The bottom thickness of the container 12 is preferably about 0.3 mm ± 0.05 mm. The distance from the magnetic field sensor 40 can be shortened to enable high-sensitivity detection, but a certain thickness is required to maintain the strength of the container 12.

(2) A rectangular wave voltage (for example, 10 Vpp, 0.277 Hz (same frequency as rotation)) is applied to the exciting coil 34 by the oscillator 32 (S102). The strength of the magnetic field applied by the rectangular wave voltage is, for example, about ± 20 Oe in the vicinity of the sample 10.

(3) A permanent magnet (for example, NdFeB magnet (dimensions 4 mm × 4 mm × 1 mm)) 38 is placed close to the container 12, magnetized for about 100 seconds, and the magnetic beads contained in the sample 10 are collected at the bottom of the container 12. (S104). The permanent magnet 38 is, for example, manually inserted into the gap between the coil 34 and the bottom of the container 12. By magnetizing with the permanent magnet 38, the magnetic beads in the container 12 are aggregated and collected in an area similar to the size of one of the sensor elements 40a and 40b, and are passed directly above the one element during rotation. ..

In this way, before the start of rotation, magnetism by the permanent magnet 38 and magnetism by the exciting coil 34 are superimposed. While applying a rectangular wave magnetic field (or a temporally fluctuating magnetic field such as a sine wave or a triangular wave) by the exciting coil 34, the permanent magnet 38 magnetizes the magnet with a permanent magnet 38 for about 100 seconds (almost in close contact). Even when the amount (volume) of the sample 10 is relatively large, the magnetic beads (including those bonded to the substance to be measured) dispersed in the sample 10 are collected at the bottom of the container 12 and the magnetism in the sample 10 is collected. By letting the beads pass in the vicinity of the magnetic field sensor, the detection sensitivity of the magnetic field sensor 40 is increased and the SN ratio is improved.

(4) Rotation is started (S106). The rotation speed is, for example, about 200 degree / s. The rotation speed should be such that the acceleration due to centrifugal force is sufficiently smaller than the gravitational acceleration because the liquid phase becomes unstable when the rotation speed is high. At the start of rotation, the magnetic field of the permanent magnet 38 and the magnetic field of the exciting coil 34 are in the same direction. Immediately before or immediately after the start of rotation, the permanent magnet 38 is removed from the position where the permanent magnet 38 is placed, and only the magnetic field of the exciting coil 34 is applied to the sample. Make it a state. The placement and removal of the permanent magnets 38 may be done either manually or mechanically.

FIG. 5 is a diagram showing the positional relationship of the sample 10 in the container 12 passing over one element of the magnetic field sensor 40. For example, when the cross-sectional diameter of the container 12 is larger than the width of one element of the magnetic field sensor 40, when the magnetic beads in the sample 10 are collected at the bottom of the container 12 by the permanent magnet 38 in the container 12, the bottom of the container 12 is collected. The aggregated magnetic beads are biased to the left and right sides and aggregated so that the aggregated magnetic beads fit within the width of one element of the magnetic field sensor 40 (sensor element 40a in FIG. 5). In FIG. 5, it is prevented from passing directly above the sensor element 40b).

(5) After the start of rotation, when passing over the exciting coil 34, the sample 10 is excited by a magnetic field (square wave) having the opposite polarity for each round (S108). After the start of rotation, the permanent magnet 38 is removed, and a rectangular wave magnetic field (about ± 20 Oe) having the same frequency as the rotation frequency is applied to apply a magnetic field in which the magnetization polarity is reversed for each rotation to the sample 10. As a result, the magnetic beads contained in the sample 10 tend to rotate in the direction of the magnetic field. At this time, if only the magnetic beads (unbonded magnetic beads that are not bonded to the material to be measured), the volume (or radius of gyration) of the magnetic beads is sufficiently smaller than that of the material to be measured, so that the relaxation time is long. It is short and magnetizes and rotates relatively easily due to the magnetic field generated by the exciting coil 34, but the magnetic beads bonded to the object to be measured have a relatively long relaxation time and are in a state where it is difficult to magnetize and rotate.

(6) The sample 10 in the container 12 passes directly above one element of the magnetic field sensor 40 after being excited by the magnetic field of the exciting coil 34 whose magnetic field direction is switched every time, for example, after 3/4 cycle, and the magnetic beads are used every time. (S110). The gap between one element of the magnetic field sensor 40 and the bottom of the container 12 containing the sample 10 is preferably about 0.1 mm. The narrower the gap, the smaller the amount of magnetic beads can be detected, and the smaller the amount of the substance to be measured (bacteria) can be detected.

Since the magnetic field sensor 40 has a differential sensor configuration, the background noise is canceled out by obtaining the difference value between the output of one element in which the sample 10 passes directly above and the other element in which the sample 10 does not pass directly above. An accurate output signal (sensor voltage value) can be obtained.

(7) The obtained sensor voltage value is arithmetically processed by the signal processing unit 50 (S112). The signal processing unit 50 obtains ΔV / V by calculation, where ΔV is the sensor voltage difference between two adjacent laps and V is the sensor voltage at the first rotation (first lap) (S112). Specifically, the sensor voltage difference ΔV _{1 on the first} and second laps, the sensor voltage difference ΔV _{2 on the second} and third laps, and the sensor voltage difference ΔV ₃ on the third and fourth laps are sequentially obtained. go. _{Then, the sensor voltage difference ΔV n} between the final nth lap and the n-1th lap is obtained, the average value ΔVave of all ΔV _k is obtained, and this is normalized by the sensor voltage V of the first lap to obtain ΔVave / V. .. The SN ratio is improved by finding and averaging the sensor voltage difference ΔV _{k a plurality of times.}

FIG. 6 is a graph showing measurement data of the output voltage of the magnetic field sensor 40. The horizontal axis shows the passing position (length) of the magnetic field sensor 40, and the vertical axis shows the output voltage of the magnetic field sensor 40. The output voltage changes depending on the position where the container 12 passes through the magnetic field sensor 40.

FIG. 6A is a measurement graph using a liquid containing only magnetic beads (average particle size is about 170 nm and does not contain polymer beads as a substance to be measured) as a sample 10, and FIG. 6B is a measurement graph. It is a measurement graph using a mixed solution of polymer beads (model bacteria, average particle size of about 7 μm (micron)) and magnetic beads as a measurement substance as a sample 10.

FIG. 6A shows the displacement of the output voltage from the first lap to the fourth lap, but in two adjacent laps, that is, when the number of laps is odd and even, the polarities are inverted to form a symmetrical shape. A close waveform can be obtained. That is, when the substance to be measured (polymer beads) is not contained, the magnetization direction of the magnetic beads is also reversed following the magnetic field whose polarity is reversed every time. Therefore, the sensor voltage difference between the odd-numbered times and the even-numbered times becomes relatively large.

On the other hand, in the graph of FIG. 6B showing the measurement results when the sample 10 contains the magnetic beads and the polymer beads, the displacement of the output voltage from the first lap to the fourth lap is an odd number of times and an even number of times. There is no big difference in the waveform. This is because the magnetic beads are bonded to the polymer beads, so that the magnetic beads cannot follow the switching of the magnetic field for each orbit and the magnetic beads are difficult to invert. It is presumed that it is difficult to get up. That is, the difference between the odd-numbered and even-numbered waveforms suggests that there is a correlation with the amount (number) of the substance to be measured.

FIG. 7 is a graph showing the relationship between the amount of polymer beads and the adjacent voltage difference. The substance to be measured is polymer beads, which are model bacteria, and the sample is a mixed solution of polymer beads and magnetic beads. The horizontal axis is the amount of polymer beads, the vertical axis is the value of the adjacent voltage difference, and the vertical axis is the value of the adjacent voltage difference, which is normalized by the voltage value of the first cycle (the voltage value “V” described above). The value is calculated, and the average value of multiple laps (ΔVave / V described above) is used. According to FIG. 7, it is clearly understood that the larger the amount of polymer beads, the smaller the adjacent voltage difference tends to be. Although the number of polymer beads in 7.5 × 10 ⁵ or more are substantially constant value adjacent times voltage difference, which is almost all of the magnetic beads bound to the polymer beads, the number of magnetic beads present alone It is thought that this is because there are not enough. When the graph of FIG. 7 is obtained in advance and the sample whose model bacterial count is unknown is evaluated, the model bacterial count can be determined from the measured adjacent voltage difference using the curve of FIG. 7 (FIG. 7). 6 S114). The signal processing unit 50 compares the measured adjacent voltage difference ΔVave / V with the graph data of FIG. 7 to determine the number of objects to be measured.

FIG. 8 is a graph showing the relationship of the adjacent voltage difference with respect to the number of caries-related bacteria (mutans bacteria). The substance to be measured is not a model bacterium but an actual bacterium, mutans bacterium, and the sample is a mixed solution of magnetic beads and mutans bacterium (Mutans bacterium). The magnetic beads used had an average particle size of about 1 micron to which Protein A was added. There are about 5 × 10 ⁷ magnetic beads in 100 microliters. First, the magnetic beads are reacted with an antibody (Anti-Streptococcus Mutans antibody Ab31181). Subsequently, Streptococcus mutans bacteria were subjected to an antigen-antibody reaction with the above magnetic beads to prepare a sample.

According to FIG. 8, as the number of Mutant bacteria increases, the adjacent voltage difference tends to decrease. It is considered that this is because the number of single magnetic beads decreases as the number of Mutant bacteria increases, and the brown relaxation of the magnetic beads is less likely to occur. When the number of Mutant bacteria is 1 × 10 ⁷ or more, the adjacent voltage difference is almost constant, because almost all magnetic beads bind to Mutants bacteria and the number of magnetic beads existing alone is sufficiently small. it is conceivable that. From this, it is estimated that about 5 magnetic beads are bound to one Mutant bacterium on average. The graph of FIG. 8 is obtained in advance, and when evaluating a sample in which the number of Mutant bacteria is unknown, the number of Mutant bacteria can be obtained from the measured adjacent voltage difference using the curve of FIG. 8 (FIG. 8). 6 S114). The signal processing unit 50 compares the measured adjacent voltage difference ΔVave / V with the graph data of FIG. 8 to determine the number of objects to be measured.

In order to detect Mutant bacteria less than in FIG. 8, the number of magnetic beads is reduced to set a range in which the amount of magnetic beads present alone changes significantly. Further, by improving the SN ratio of the magnetic field sensor 40, it becomes possible to detect less Mutant bacteria.

In the embodiment of the present invention, a liquid containing a magnetic substance (magnetic beads) and an object to be measured that can be bonded to the magnetic substance (magnetic beads) is rotated, and a magnetic field whose polarity is reversed every time the circumference thereof is applied to cope with the change in magnetism. The output signal can be detected for each lap, and the amount of the object to be measured can be measured by using the difference in the output signals of the adjacent laps, so that a more sensitive magnetic immunological test can be performed.

The present invention is not limited to the above-described embodiment, and there are design changes within a range that does not deviate from the gist including various modifications and modifications that can be conceived by a person having ordinary knowledge in the field of the present invention. Of course, it is also included in the present invention.

10: Sample, 12: Container, 20: Rotating mechanism, 22: Table, 24: Rotating shaft, 26: Arm, 30: Magnetic field generator, 32: Oscillator, 34: Exciting coil, 38: Permanent magnet, 40: Magnetic field Sensor, 40a: Sensor element, 40b: Sensor element, 42: Bias magnet, 44: Magnetic shield, 50: Signal processing unit

Claims (9)

A magnetic field measuring device for detecting an object to be measured by a magnetic immunological test.
A moving mechanism that orbits a container containing a sample containing a magnetic substance and the object to be measured that can be bonded to the magnetic substance.
A magnetic field generator for applying a magnetic field to the magnetic field direction changed by inverting the each cycle in synchronization with the rotation period of the vessel, the sample contained in the container orbiting,
A magnetic field sensor that detects a signal corresponding to the magnetic field emitted from the sample housed in the orbiting container, which is arranged at a position separated so as not to be substantially affected by the magnetic field generated from the magnetic field generating portion. Equipped with
The magnetic field sensor includes two sensor elements arranged in parallel in a direction orthogonal to the rotation direction of the container, and a bias magnet for applying a bias magnetic field to the sensor element.
The moving mechanism is such that the magnetic substance collected and aggregated in the container and the object to be measured bonded to the magnetic substance pass directly above one of the sensor elements and do not pass directly above the other. A magnetic field measuring device characterized by orbiting a container. Magnetic field according to claim 1, characterized in that it comprises a plurality of times determining arithmetic processing unit the amount of the object to be measured based on the difference value of the signal detected by the orbiting of the adjacent two of the circulation of the measuring device. The magnetic field measuring device according to claim 1 or 2 , wherein the magnetic field sensor is a magnetic impedance sensor. Between the container orbiting and said bias magnet, the magnetic field measuring apparatus according to any one of claims 1 to 3, characterized in that the magnetic shielding means is arranged. The invention according to any one of claims 1 to 4 , further comprising a magnetizing magnet for magnetizing a sample housed in the container by a DC magnetic field, wherein the magnetizing magnet is removed when the container rotates. Magnetic field measuring device. It is a magnetic field measurement method for detecting an object to be measured by a magnetic immunological test.
A step of magnetizing a sample containing a magnetic substance and the object to be measured that can be bonded to the magnetic substance by a DC magnetic field using a magnetizing magnet.
The process of rotating the container containing the sample multiple times by the moving mechanism, and
By the magnetic field generating unit, and applying a magnetic field to the magnetic field direction in each cycle in synchronization is switched by reversing the rotation cycle of the container, the sample contained in the container orbiting,
The magnetic field sensor comprises a step of detecting a signal corresponding to a magnetic field emitted from a sample housed in the orbiting container.
The magnetic field sensor includes two sensor elements arranged in parallel in a direction orthogonal to the rotation direction of the container, and a bias magnet for applying a bias magnetic field to the sensor element.
The moving mechanism is such that the magnetic substance collected and aggregated in the container and the object to be measured bonded to the magnetic substance pass directly above one of the sensor elements and do not pass directly above the other. A magnetic field measurement method characterized by orbiting a container. Magnetic field measuring method according to claim 6, characterized in that it comprises a plurality of times step of determining the amount of the object to be measured based on the difference value of the signal detected by the orbiting of the adjacent two of the circulation of the .. The magnetic field measuring method according to claim 6 or 7, wherein the magnetic field sensor is a magnetic impedance sensor. The magnetic field measuring method according to any one of claims 6 to 8, wherein a magnetic shielding means is arranged between the rotating container and the bias magnet.

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